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BT-001 in solid tumors

Target: CTLA-4, GM-CSF Status: Phase 1 Partner: Transgene


MABS + Oncolytic virus to target solid tumors

Project status and outlook
IND approval from the FDA
In May 2021, the Investigational New Drug (IND) application for BT-001 was granted by the U.S. Food and Drug Administration (FDA). The IND will allow patients in the U.S. to be enrolled into the ongoing Phase 1/2a clinical trial. Since March 2021, patients are enrolled to the ongoing Phase 1/2a open-label, multicenter, dose-escalation study evaluating BT-001 as a single agent and in combination with pembrolizumab. The study (NCT04725331) is currently enrolling patients at sites in France and Belgium. The first Phase 1 data is expected H1 2022.

Evaluating the safety and tolerability
The overall objective of the Phase 1/2a study is to evaluate the safety and tolerability of BT-001 alone and in combination with pembrolizumab. The ongoing Phase 1 component of the study is divided into two parts: Part A will evaluate intra-tumoral injections of BT-001 as single agent in up to 36 patients with advanced solid tumor disease. Part B will explore the combination of intra-tumoral injections of BT-001 with pembrolizumab in several cohorts of 12 patients each.

Exploring the activity in Phase 2a
The subsequent Phase 2a component of the study will evaluate the combination regimen in several patient cohorts with different tumor types. These expansion cohorts will offer the possibility of exploring the activity of this approach to treat other malignancies not traditionally addressed with this type of treatment.

Out-licensing and partnering
Since 2017, BioInvent and Transgene collaborate on the development of oncolytic virus (OV) drug candidates aimed at treating solid tumors, with the potential to be significantly more effective than the combination of a virus and an antibody as single agents. The clinical drug candidate BT-001 encode both an differentiated and proprietary anti-CTLA-4 antibody and the GM-CSF cytokine.

Transgene is contributing its proprietary oncolytic virus (OV) platform Invir.IO™, designed to directly and selectively destroy cancer cells by intracellular replication of the virus in the cancer cell (oncolysis). Oncolysis induces an immune response against tumors, while the “weaponized” virus allows the expression of genes carried by the viral genome, here an anti-CTLA-4 antibody, which will further boost immune response against the tumor.

The research and development costs, as well as revenue and royalties from drug candidates generated from the collaboration, are shared 50:50.

BT-001 is a best-in-class oncolytic virus developed with Transgene’s Invir.IO™ platform, engineered to encode both a Treg-depleting human recombinant anti-CTLA- 4 antibody generated by BioInvent’s proprietary n-CoDeR®/F.I.R.S.T™ platforms, and the human GM CSF cytokine.

The use of an oncolytic virus to deliver the anti-CTLA-4 locally and selectively in the tumor microenvironment allows high intratumoral concentrations, eliciting a stronger and more effective antitumor response. By reducing systemic exposure to a very low level, this local therapeutic activity furthermore allows to increase the safety and tolerability profile of the anti-CTLA-4 antibody.